The term “extremophilic microbes” cover organisms belonging to all the domains of archaebacteria and other prokaryotic organisms, as well as eukaryotic microorganisms, such as certain fungi. All of these organisms prefer to live and flourish in extreme conditions. In all probability, they colonized the Earth far before any of the more complex forms of life that succeeded them. The reason for their success at thriving in extreme environments is often their well-adapted physiology in tandem with the enzymes that they release in response to these extreme conditions called extremozymes. These extremozymes possess advantageous properties such as heightened stability and catalytic efficiency under varied parameters such as pH, temperature, pressure, salinity, light, radiation, and water content. This chapter covers the role of extremophiles and their enzymes (extremozymes) in various domains such as biofuel generation, therapeutics production, biofertilizers, and in bioremediation of various environmental pollutants.